 Okay. So, I know that the title of the talk was originally Outcomes in Cardiomyopathy, but it's really difficult to talk about just outcomes without also mentioning medical therapy. So while a lot of this talk is going to be review of, you know, good bread and butter, heart failure, what you do with medications, some review of the evidence, there has been a little bit of new research done recently with a couple new medications and we'll talk about appropriate use for those. And then some special situations in which cardiomyopathy involves particularly women and where if you recognize and treat in specific ways a little earlier, you really have an impact on outcome and improving outcome. So you heard a little bit earlier, I'm sure Dr. Nyer talked a little bit about the differences between the types of heart failure and really you have to look at the classification when you're talking about medical therapy, which is there's heart failure with reduced ejection fraction versus preserved ejection fraction. And quickly we talk about HEF-REF or HEF-PEF. Specifically HEF-REF is when the ejection fraction is less than 40% and in HEF-PEF it's generally accepted that the ejection fraction is above 50%. And the interesting thing is that despite all of the trials and evidence and all the research we've done, most or pretty much all of our proven therapies are for HEF-REF and there's really a lack of proven therapies for HEF-PEF, which makes it very difficult to treat. Specifically in my talk I'm going to focus more on HEF-REF and they've been a recent set of guidelines for the treatment of heart failure. Most recently there was an update in 2016 but the main guidelines were found in circulation in 2013. So I'd refer you to that as the main reference for this talk. So in general there's about one in five people in the U.S. will develop heart failure. There is earlier onset in men. HEF-PEF is actually equal among women and men though it's more common overall than HEF-REF and that might be because we're diagnosing it more you know since it's a little bit more recognized now probably in the last decade. Overall HEF-REF is more common in men. Over the last 20 years overall there's been a reduced incidence of heart failure however there's an increased percentage of patients with heart failure being classified as HEF-PEF and those HEF-PEF patients have higher rates of hospitalization and overall there's been an increase in the mortality rate from heart failure specifically for HEF-REF and something that's important to know especially as you're thinking about where your patients are in the spectrum of what kind of therapy they need the number of hospitalizations in the last one year is very predictive of their outcome and we know that if you have two or more admissions in one year the mortality increases to about 50% mortality. There are some special populations when we're talking about heart failure in particular African Americans and women about 3% of the African American population eventually develop hypertension and most frequently that I mean sorry heart failure and most frequently that has to do with hypertension and it should be noted that across all nationalities hypertension is the number one risk factor for development of heart failure with preserved and with reduced ejection fraction. In African Americans heart failure happens at an earlier age of onset and it's usually more advanced at the time of diagnosis they do overall have higher rates of hospitalization and a much higher mortality rate and then the other special population is women and that's mainly because although they respond to therapy the same as men there are some particular situations in which women develop cardiomyopathies like peripartum cardiomyopathy which I think you heard about earlier and also chemotherapy induced cardiomyopathy specifically because of the prevalence of breast cancer in women but also because there's some research into the way women respond differently to chemotherapy and makes them a little bit more susceptible to chemotherapy induced cardiomyopathy. It's important to note that when we're talking about medical therapy and outcome the guidelines are based on the classification and when you start different types of medicines is based on the clinical status of the patient and so you'll often see these two different types of classification systems the AHA and the NYHA class and so just to review that for you all there's AHA stages A, B, C and D. Stage A is someone who's at risk for heart failure classically that's someone who has things like hypertension and other cardiac risk factors and just to remind you that hypertension is the number one risk factor for development of heart failure and then I put on there this thing called obesity paradox which is something interesting which it has been shown that patients who develop heart failure who happen to be obese actually have better outcomes than people who are thinner and we don't really know why. AHA stage B are patients who have known structural heart disease but don't actually have clinical heart failure so they don't have any exertional symptoms they're not admitted to the hospital with fluid overload you just know that they have the anatomical setup. Stage C is clinical heart failure and stage D is refractory and stage disease these stage D patients are the ones who are on inotropes having L-vads and talking about transplant or listed for transplant and then there's NYHA class which has generally been shown to be the most predictive of overall mortality and the higher the NYHA class the worse the outcome. So class one is they have no limitation of activity or symptoms with exertion they can do whatever they want to do they just happen to have a low ejection fraction. Class two is they have a slight limitation usually these patients are comfortable at rest but they do have some symptoms like exertional dyspnea with some activity. Class three they have marked limitation they're comfortable at rest but with minimal activity they get very symptomatic and then class four is rest symptoms. So when we're talking about medical therapy for heart failure in the literature we kind of use this catchphrase guideline directed medical therapy and these are the medications when we talk about guideline directed medical therapy for heart failure to improve morbidity and mortality these are the medications that we're talking about so I'm just going to kind of run through them real quickly ones that you've been familiar with for a while. The first is a beta blocker which has a 1a indication it improves mortality more benefit sorry morbidity and also has been shown to improve LV remodeling and improve the LVEF. In beta blockers you want to start them prior to hospital discharge this was shown very clearly in the impact heart failure trial the only caveat to this is if the patient required inotropes during that admission you want to be a little a little bit more cautious with starting beta blockers before their discharge and specifically the medications that have been shown to be evidence-based beta blockers in the setting of heart failure are curvetolol besoprolol and metoprolol succinate okay so you might see a patient that comes to see you and they have heart failure with a reduced ejection fraction and you see they're on metoprolol tartrate or a tenolol you really want to switch them to an evidence-based beta blocker because those are the ones that have been shown to actually have these positive impacts on outcomes. The second type of medication are ACE inhibitors that also has a class 1 indication for patients with HEFREF it improves their mortality their morbidity and their symptoms and there's a 1a indication for an ARB as first line if the patient is ACE intolerant but you can only use it as first line therapy that's really a 2a indication so the guidelines still want you to try an ACE first unless you have a good reason like ACE intolerance which would be like an ACE cough so then you can start with an ARB as first line therapy and then the other 1a indication is aldosterone receptor antagonists so spironolactone or a plurinone and those are 1a indications in patients who have symptomatic heart failure with an ejection fraction less than 35% or if they have coronary disease and they have heart failure from coronary disease so ischemic cardiopathy and their EFs less than 40 and diabetes you want to go ahead and make sure that they're on an aldosterone receptor antagonist and then these patients and specifically you want to make sure that their creatinine is less than 2.5 in men or less than 2 in women before starting it and their potassium is less than 5 there's been there's an interesting curve when the studies came out showing that aldosterone receptor antagonists were beneficial in heart failure there was a significant increase in the amount of people going to the hospital with hyperkalemia because they were starting they were getting started on it with either their creatinine a little too high or at baseline you know adding it to the ACE or the ARB your K can go up so when you make this change you want to make sure that at least in the next two weeks one to two weeks after starting the medicine you recheck their labs make sure their potassium is not becoming too high and you want to be really careful with having them on potassium supplementation if they're on all these medicines at once so we know and there's been there's been a lot of trials supporting these medications this data is from meta analysis but basically if you combine all of the 1a indication medications you see the relative risk reduction in mortality which each medication so with a beta blocker you decrease their mortality by 35% an ACE 23% an aldosterone antagonist 30% then we didn't really talk about cardiac resynchronization therapy but 36% and so if you do all of these therapies together you get a 77% risk reduction and basically the number needed to treat to prevent one death is four so that's overwhelming evidence to use these medical therapies and all of your heart failure patients with reduced ejection fraction a little bit on some of the newer medications just to reiterate because there is a little bit of confusion I've just seen amongst cardiologists in the community is when to use some of these newer agents these specifically were addressed in the recent 2016 guideline updates for heart failure but basically there's two new medications on the market right now for heart failure reduced ejection fraction the first is an ARNI you guys know it as intresto it now has a 1b indication for symptomatic heart failure patients who are already tolerating an ACE or an ARB and you can replace those ACE or ARBs by this ARNI to further reduce their morbidity and mortality okay the key to this is that the patient symptomatic so it's really not for patients who have NYHA class 1 heart failure okay and they also note that you want to make sure that you have at least a 36-hour washout phase so when you decide okay I've got this you know NYHA 2-3 patient they're on the guidelines are that they have it they can tolerate at least 10 milligrams of an alapyril twice a day you decide to make the switch you stop the ACE or ARB you give them 36 hours then you start the intresto the other new medication is evaporidine or corlonore and it has a 2a indication in patients with symptomatic heart failure who are currently on maximally tolerated doses of beta blockers and in sinus rhythm which is key but still have a heart rate above 70 percent sorry 70 beats per minute and this medication has been shown to reduce heart failure admissions other parts of medical therapy that we should all consider for our heiferous patients hydrolysine nitrate combination this has been shown to have a mortality benefit in African-Americans with very symptomatic heart failure so stage 3 and 4 and it's used in combination with a beta blocker and an ACE inhibitor you can use it a little earlier in patients who are intolerant to Acer ARBs because they say they get hypotensive with other medical therapy or they have advanced renal disease and it it precludes them from being on an Acer and ARB and then finally did joxin one of the oldest heart failure medications that we have it has been shown to reduce the risk of heart failure hospitalizations but it only has that morbidity benefit it doesn't have a mortality benefit it still has a 2a indication and a lot of this data was actually done before even the beta blocker trials but it's not going to be repeated so I think it's always going to have this 2a indication it has been shown though that withdrawal of digoxin can precipitate a heart failure decompensation so you want to be careful if you have a patient who's been on ditch for a long time and they come in and you decide to stop it or someone stops it in the hospital it can be detrimental down the road and then finally diuretics they have a 1c indication pretty much all of us who have heart failure patients know they usually are on a little bit of diuretic the mainstay of therapy is loop diuretics and in general if someone comes in when the acute exacerbation the guidelines say that you want to double the dose and consider giving it IV there has been something in a lot of dose trial which basically showed that there's no difference between intermittent high dose versus continuous infusion so you don't have to put everyone on a lacyx drip or a bumex drip just just hit them hard with it intermittently and that you know will get you the same effect and then there's always metolazone uses a booster I find it very effective in patients who have some higher creatinine and are really holding on to fluid you just have to be really careful with hyper hypokalemia because even if they have renal disease these are the patients if you're having them on a lot of metolazone that they're going to end up meeting potassium replacement even if their creatinine is elevated and then another one that I think is important to mention is anti-coagulation because in the past there was a tendency that if people have a very low ejection fraction like less than 20% there was always this kind of question like should we put them on blood thinners what if they have an apical aneurysm is part of that maybe you know basically it's been shown in several trials that it's it's contraindicated unless you have another reason to put them on anti-coagulation so unless the patients have AFib they have a prior thrombotic event or they have a known LV apical thrombus you don't empirically put people with low ejection fractions on warfarin you it's too high of a risk of bleeding so I think it's helpful to talk about the way we can classify cardiomyopathies in general when we're talking about heffereff we apply these medications across all spectrums of heffereff but there are some particular etiologies of cardiomyopathy that we can handle in a little bit of a different way and also have different outcomes than just the general run of the mill so in general we're talking about cardiomyopathy there's genetic mixed and acquired genetic is things like Hocom, ARVC, LV non-compaction, some of the ion channel disorders there's this mixed bag of dilated and restrictive cardiomyopathies and among the dilated cardiomyopathies about about half of them are ischemic and in that 37 percent other a lot of that ends up being a familial cardiomyopathy if we go through all the genetic testing and then acquired things like myocarditis, tachysubo, peripartum, and tachycardia induced so some special populations I just wanted to touch on because they have interesting and often better outcomes than just general run of the mill heffereff the first being alcohol mediated cardiomyopathy it's important to remember that just being a drinker you know their patient comes in they have a dilated cardiomyopathy and they say they drink you know three beers a day that's really not enough you can't say oh it's because of your alcohol intake this requires a high amount of alcohol consumption so an average greater than five drinks a day for many many years before you can really say that it's due to the alcohol and really with abstinence and alcohol use and good heart failure medication you often see a significant improvement and normalization of the LV function the other type of cardiomyopathy that you can see a very good outcome with just control is tachycardia mediated usually this heart rates consistently above 110 beats per minute and it's very rarely with sinus tachycardia so this occasional inappropriate sinus tachycardia patients you see you really don't have to worry about them developing developing a cardiomyopathy the way you do your patients with chronic aphid with RVR it is reversible with heart rate control the only variation being if someone has a cardiomyopathy because of frequent PVC's and they get a 24-hour halter monitor and they have more than 20% of their beats in that 24-hour period being PVC's you really need to refer them for a PVC ablation in order to see an improvement in their LV function so these are two types of cardiomyopathy that with basically either withdrawal of the withdrawal of the offending agent or heart rate you can see a pretty much normalization of their LV function and a really good outcome the other type is peripartum cardiomyopathy I know you heard a lecture on this earlier so I'm just going to touch on it but basically it's diagnosed one month prior to delivery up to five months post and it really has a very good chance of recovery quoted as 50 to 60% of these patients recover with good medical therapy about 25% of them go on to have stable heart failure and about 25% will actually go on to either have progressive heart failure and require transplantation the risk factors is older age multi-parity multiple gestations preeclampsia or hypertension and then the use of beta agonist to delay labor chemotherapy induced cardiomyopathy this type of cardiomyopathy it doesn't have the best type of outcome it's I wanted to mention it specifically because we see it a lot more in women specifically patients who have chemotherapy with anthrocycline's duck's rubison is most commonly used as part of the chemotherapy for breast cancer and also a lot of hematologic malignancies and also then one of the newer agents trust use a map for breast cancer in those types of cancers especially breast most of the patients are women however as I mentioned before there is this evidence that it seems as though women even those who are getting it getting this type of chemotherapy not for just breast cancer they tend to develop higher rates of cardiomyopathy and it seems like women for whatever reason are more sensitive to the myocardial toxic effects of chemotherapy overall this type of cardiomyopathy has a much worse prognosis than the other types of heffreff and it's very important that these patients have an earlier diagnosis and thus earlier chance to get started on this guideline directed medical therapy to increase their chances of having LV recovery it's pretty much been shown in several studies that if the patient gets started on therapy within six months of the development of the cardiomyopathy they do much better and then if they get started on therapy more than 12 months after the development of the cardiomyopathy it's very unlikely and nearly 0% chance that they'll have any improvement in their heart failure so a lot of places now I've developed these departments of cardiomyocology where patients get echoes after every cycle of chemotherapy to see if they've had changes in their LV function to help guide the oncologist and best how to treat them specifically for anthracycline based chemotherapy it's dose-dependent for Tresc Duzumab once you see the ejection fraction drop you can actually withdraw the agent see the EF normalize and then you can restart it safely and overall these patients have an increased incidence of right ventricular dysfunction and along with left ventricular dysfunction and so that can be an important consideration should they need advanced therapy down the road like an LVAD they have much higher rates of needing right-sided support like a BIVAD or a temporary RVAD when they go for mechanical support so that definitely impacts their outcomes and then another special population that pretty much has a pretty poor outcome but you can try to step in a little earlier to change that is sarcoid classically on the pathology you see non-KC and in gramulomas it's usually a dilated cardiomyopathy they often present with conduction blocks because the sarcoid tends to involve the intraventricular septum where the electrical pathways are they classically have aneurysm formation in weird areas of the myocardium as you can see on this echo they have it in the septum in the inferior lateral wall not not always in the apex a lot of the patients will be of Scandinavian descent sometimes Japanese and African-Americans diagnosis with biopsy you can also see it with some changes on MRI and then you can also see the amounts and activity of sarcoid in FDG pets you treat it with steroids but in patients with advanced sarcoid 80% of the death is due to cardiac disease so it's actually recommended that if you have a patient with sarcoid you at least screen them for heart involvement and the easiest way to do that is either an MRI or an FDG pet which they do that here and another one to be kind of aware of is giant cell myocarditis these people present very dramatically they come in in fulminic, cardiac and shock they often have elevated biomarkers but not always they have very unstable arrhythmia is VT storm is also something that they'll present with you diagnose diagnosis with a biopsy or with an MRI and you basically blast them with steroids plus or minus IVIG and you'll see them turn around really fast but that's the important thing because if you don't catch it you'll see them go the other way very quickly because they're so unstable a lot of these patients will require temporary ECMO support to get them through the period until they recover and then something that's important to know is in these patients when they recover they a lot of you know when they do make it through they say what do I do now what can I do well they can do pretty much anything but no competitive sports for three to six months and actually had a patient on like this a few weeks ago as a 19 year old she just like showed up in the hospital and we put on ECMO and hit her with steroids and she walked out of the hospital and that was incredible another particularly interesting type of cardiomyopathy is left ventricular non-compaction these patients it's a genetic disease really not sure of all the genes involved and what makes people progress to heart failure because in the community you can see patients who have LV non-compaction but have normal ejection fraction they do have possibly an increased risk of sudden cardiac death they should not participate in competitive sports that's important when you're counseling your patients who have LV non-compaction no competitive sports if they have an ejection fraction less than 35% they should be placed on warfarin it for full anti-coagulation to prevent formation of thrombi and these little crevices in their LV and it's also important to know the indications for ICD for these patients which includes a family history of sudden cardiac death if they have lots of non-sustained matricular tachycardia on monitoring if their EFs less than 35% and also if they have unexplained syncope and then finally arithmetic right ventricular cardiomyopathy you know a classically this involves men as in a three-to-one ratio but women are diagnosed with this you know occasionally and it's important to remember for them that you also have to advise them and their first-degree relatives that they cannot be active in sports this is a really recognized cause of sudden cardiac death and athletes but it doesn't have to be if we can pay attention to our patients screen them you see this classic Epsilon wave on their EKG so just something to keep in your back of your mind as you're seeing patients so I have just a few questions so we'll kind of test some knowledge so the first question is it'll just be free answer just call out what you think cancer is so there's a 45 year old African American woman with breast cancer and she has had anthracycline based chemotherapy with her last dose given three months ago and she was diagnosed with chemotherapy induced cardiomyopathy with an EF of 25% she does have some fatigue and dyspnea with climbing you know even a few stairs which initial medications would you prescribe so let's go through the options would you put her on metoprol tartrate and lysine a pearl carvetolol and low sartan carvetolol and lysine a pearl or hydrolyzing our schedule combination and lysine a pearl so you know you want to put her on your good guideline directed medical therapy so that includes a beta blocker right first line beta blocker 1a it should all be on beta blockers and we want to use those evidence-based beta blockers so is metoprol of tartrate one of those no so carvetolol and then I haven't given you any evidence that she's ace intolerant and so 1a also an ace so the answer here would be carvetolol and lysine a pearl okay and even though she's symptomatic she's not not yet done on any other medical therapy so you wouldn't jump first to the hydrolyzing isotope combination that's more for class 3 4 heart failure if they're already tolerating their guideline directed medical therapy but still symptomatic okay any questions about that question question to the same patient comes you a year later and you do an echo and her EF is now 55% yay and she asked can she stop her medications because they're kind of a hassle for her to take every day and what do you tell her no yeah sorry so we kind of talked about that she cannot discontinue either medication okay you want to keep her on those watch her watch her LV function and you still want to kind of try to titrate her medications as well question 3 69 year old man with coronary disease and ischemic cardiomyopathy has an EF 30% he's on his guideline directed medical therapy with long-acting metoprol, captupril and a plurinum his resting heart rates 85 and his blood pressure is 110 over 65 he can climb stairs at home without any dyspnea or chest pain and he doesn't have any edema so he's feeling pretty good what changes to his medications do you recommend so my first question is which NYHA class is this patient he can climb stairs he doesn't have any symptoms when he exerts himself he's a one okay so he's an NYHA one he's on a beta blocker an ACE inhibitor and aldosterone receptor antagonist his heart rates 85 his blood pressure is 110 over 65 so do we make no changes he's doing great keep doing what you're doing do we stop his captupril and start in teresto do we increase his metoprolol do we start coronary what you guys think so this one this one's a tricky question it has a few a few extra things in it so the answer is you want to increase his metoprolol succinate okay so the key to this question the root of it is even though people are doing well you want to try to maximize their medications because you're gonna get the best bang for your buck at the highest doses that they can tolerate okay and you know that he needs higher dose because his heart rates 85 and that's not really goal you really want their heart rate to be less than 70 okay and so and I you know I try to tricky a little bit his blood pressure is 110 over 65 that's fine if someone's EF is 20% they don't need a blood pressure of 120 over 80 and really you don't want it to be that high you want them to be down in like the 100s the 90s as long as they're not dizzy put push the meds okay so and you don't want to use in teresto because like I said in teresto is reserved for patients who has symptomatic heart failure so NYHA class two and three okay we're all kind of tempted to use the newer fancier things but the good old-fashioned heart failure medications are really what you go for first and then you wouldn't use coral and ore because they're currently not on maximally tolerated doses of beta blocker okay questions about this question in which patient with heff ref would you add hydrolyzing nitrate combination a white man with a class three heart failure who's already on an ace in a beta blocker a white woman class three heart failure who's not yet on medical therapy an African-American man who has class three heart failure is hypertensive and not yet on therapy an African-American woman class two heart failure who's on an ace in beta blocker already or an African-American man who has class three heart failure who is already on an ace in a beta blocker we're hearing C E okay E good so we know that we use hydrolyzing nitrate combinations in predominantly African Americans that's when the data is patients who are on the guideline directed medical therapy with an ace or an arm and a beta blocker and still symptomatic which is class three or four so you're exactly right last question 55 real women's refer to you after diagnosis of dilated non-eschemic cardiomyopathy and you look at her echo and these are still images for you and this is what we see in her echo anyone notice thing particular dr. Colton sees this a pointer so actually here and then this is short axis here what is this what is she what kind of cardiomyopathy does she have lb non-compaction good so she has mild fatigue while at work she's a nice this is my this is an actual patient I have by the way she's an ICU nurse she has some dyspnea when climbing stairs no one in her family has ever had sudden cardiac death and she's never passed out before she came to see you her referring physician had already done a halter monitor on her and she didn't have any arrhythmia is no non-sustain vitricular tachycardia and so you're going to start around good medical therapy with Carvetta law and Lysin April and what else should you recommend now remember oh I didn't tell you this but her EF is 20% she's just getting started on medical therapy yes her we'll say her qrs her qrs duration is 150 intresto warfarin hydrolysis and estradiol or should you put it in ICD or some combination of the two but single best answer so she's new to medical therapy and what NYHA class is she I'd say she's a two so class two new to medical therapy you just started Carvetta law and Lysin April I'm trying to give you that she doesn't have any of the scary scary risk factors to tell you that you have to jump to an ICD okay and remember we we put ICDs in patients unless they have some immediate indication we give the 90 days of medical therapy before we do the ICD so it's not a CD will we give her intresto now probably not because we're just starting her medical therapy same with hydrolysis and estradiol we do that if they're already trying to get tolerating medications so the answer is warfarin she has LV non-compaction her EF is less than 35% she is at risk of developing murals from by in those little crevices and so the key to this is just to remind you the patients with LV non-compaction with EF of less than 35% unless they have an incontraindication should be on full anti-coagulation with warfarin to prevent them from having streaks that's a hard one I can't I can't quote you evidence on that you'd have a lower yeah yeah but I will tell you that this is my patient and her LV function has improved and she is not getting an ICD at least right now so it's possible I have another though I have another patient though who's a man who has LV non- compaction and his LV function isn't going anywhere so I mean yeah yeah well and the hard thing was to her echo wasn't really that obvious that she had LV non-compaction so I sent her for an MRI and that was very clear that she had non-compaction and the EF on her MRI after night and I actually had been a while she got a medical therapy